This application proposes to study some aspects of the morphogenesis, differentiation and cell proliferation of the endocrine pancreas. In the late gestation, the pancreatic islet cells are believed to derive from both proliferation of differentiated islet cells and from differentiation of undifferentiated epithelial cells. It is the first objective of this proposal to study the extent of contribution of these two morphogenetic factors in the shaping of the final population size of the various cell types of islets. The quantity of the mass and the 3H-thymidine labeling index of the various cell types throughout the development of the rat from late fetal through neonatal to adult ages will be assessed. Functionally, the fetal islets are incapable of responding to glucose stimulation to produce a larger amount of insulin. It is the second objective of this proposal to reexamine whether this unresponsiveness to glucose is due to immaturation of insulin synthesis or release mechanism or both. This is done by studying the 3H-leucine incorporation into insulin and proinsulin and by measuring the insulin released in the incubation fluid by radioimmunoassay. The glucose is known to cause islet hyperplasia both in vivo and in vitro. It is the third objective of this proposal to quantitatively characterize the effect of glucose on the proliferation activity of beta cells. The effect is measured by 3H-thymidine labeling index and incorporation of 3H-thymidine radioactivity in the explanted pancreatic pieces.